Dendrimer‐Like Supramolecular Assembly of Proteins with a Tunable Size and Valency Through Stepwise Iterative Growth

Abstract

The assembly of proteins in a programmable manner provides insight into the creation of novel functional nanomaterials for practical applications. Despite many advances, however, a rational protein assembly with an easy scalability in terms of size and valency remains a challenge. Here, a simple bottom-up approach to the supramolecular protein assembly with a tunable size and valency in a programmable manner is presented. The dendrimer-like protein assembly, simply called a "protein dendrimer," is constructed through a stepwise and alternate addition of a building block protein. Starting from zeroth-generation protein dendrimer (pG 0 ) of 27 kDa, the protein dendrimer is sequentially grown to pG 1 , pG 2 , pG 3 , to pG 4 with a molecular mass of 94, 216, 483, and 959 kDa, respectively. The valency of the protein dendrimers at the periphery increases by a factor of two after each generation, allowing a tunable valency and easy functionalization. The protein dendrimers functionalizes with a targeting moiety and a cytotoxic protein cargo shows a typical feature of multi-valency in the avidity and a highly enhanced cellular cytotoxicity, exemplifying their utility as a protein delivery platform. The present approach can be effectively used in the creation of protein architectures with new functions for biotechnological and medical applications.

Bioluminescent detection of viral surface proteins using branched multivalent protein switches

“…To arrive at sensitive viral antigen tests that at the same time fulfill the main POC requirements (fast, simple-to-use, homogeneous detection), the multivalent presentation of viral surface proteins can be exploited by constructing biosensors that bind to multiple, potentially different target proteins on the virus surface, which would allow a more specific detection of virus variants depending on the targeted HA and NA subtypes. Systems with higher valency could also be constructed by including multiple SpyCatcher and DogCatcher domains in the scaffold and mixing them with binders 39 . These sensors might even allow the direct detection of intact, infectious virus using simple readout in a homogeneous test at the point-of-care.…”

Tailored Functionalized Protein Nanocarriers for Cancer Therapy: Recent Developments and Prospects

“…The programmable assembly of protein nanoparticles could provide a route for the construction of innovative functional nanomaterials for potential applications in nanomedicine. Bae et al applied a bottom-up method to construct supramolecular assemblies of protein nanoparticles with programmable size and valency [ 104 ]. The protein was assembled into dendrimer-like nanostructures, called “protein dendrimers”, using three genetic fusion proteins (one core and two building-block proteins) ( Figure 7 A).…”

“…SnoopLigase stimulates the formation of isopeptide bonds between antigen-SnoopTagJr and IMX-DogTag. ( A ): Reproduced with permission from [ 104 ], Copyright 2021 Advanced Science published by Wiley-VCH GmbH. ( B ): Reproduced with permission from [ 108 ], Copyright 2019 Springer Nature.…”

Iterative SuFEx approach for sequence-regulated oligosulfates and its extension to periodic copolymers

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